title: Differential expression of glutamate decarboxylase messenger RNA in cerebellar Purkinje cells and deep cerebellar nuclei of the genetically dystonic rat.
abstract: The genetically dystonic rat exhibits a motor syndrome that closely resembles the human disease, generalized idiopathic dystonia. Although in humans dystonia is often the result of pathology in the basal ganglia, previous studies have revealed electrophysiological abnormalities and alterations in glutamate decarboxylase, the synthetic enzyme for GABA, in the cerebellum of dystonic rats. In this study, we further characterized the alterations in cerebellar GABAergic transmission in these mutants by examining the expression of the messenger RNA encoding glutamate decarboxylase (67000 mol. wt) with in situ hybridization histochemistry at the single cell level in Purkinje cells and neurons of the deep cerebellar nuclei. Glutamate decarboxylase (67000 mol. wt) messenger RNA levels were increased in the Purkinje cells and decreased in the deep cerebellar nuclei of dystonic rats compared to control littermates, suggesting opposite changes in GABAergic transmission in Purkinje cells and in their target neurons in the deep cerebellar nuclei. In contrast, levels of glutamate decarboxylase (67000 mol. wt) messenger RNA in the pallidum, and of enkephalin messenger RNA in the striatum, were unaffected in dystonic rats. The data indicate that both the Purkinje cells and GABAergic neurons of the deep cerebellar nuclei are the site of significant functional abnormality in the dystonic rat.
authors.affiliation: Department of Pharmacology, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: L
authors.initials: L
authors.lastname: Naudon
authors.forename: J M
authors.initials: JM
authors.lastname: Delfs
authors.forename: N
authors.initials: N
authors.lastname: Clavel
authors.forename: J F
authors.initials: JF
authors.lastname: Lorden
authors.forename: M F
authors.initials: MF
authors.lastname: Chesselet
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000201:enzymology; D002529:Cerebellar Nuclei / Q000201:enzymology* / Q000473:pathology; D004421:Dystonia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004745:Enkephalins / Q000096:biosynthesis; D005917:Globus Pallidus / Q000201:enzymology; D005968:Glutamate Decarboxylase / Q000096:biosynthesis*; D017403:In Situ Hybridization; D008970:Molecular Weight; D017072:Neostriatum / Q000201:enzymology; D011689:Purkinje Cells / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D004745:Enkephalins; D012333:RNA, Messenger; D005968:Glutamate Decarboxylase